Short-term effects of transcutaneous auricular vagus nerve stimulation on T-wave alternans in people with focal epilepsy - An exploratory pilot study.

High levels of T-wave alternans (TWA) are linked to an increased risk of sudden cardiac death. People with epilepsy display elevated TWA levels that are decreased by chronic vagus nerve stimulation via implanted devices after 2-4 weeks or later. Our objective was to explore short-term effects of transcutaneous auricular vagus nerve stimulation (tVNS) on TWA. Five patients (3 female) with focal epilepsy undergoing video-EEG monitoring were included. TWA levels were determined using a one-channel modified lead I ECG via an open-source TWA-algorithm on two consecutive days, 1 h before, during and after tVNS via the left auricle. Data are given as mean ± SE. Mean TWA at baseline was 3.8 ± 0.4 µV and 3.0 ± 0.6 µV during stimulation on day 2. Stimulations on the second day were associated with TWA reductions by 22 ± 13 % that exceeded stimulation effects on the first day relative to baseline (p < 0.05). Linear mixed-models revealed effects of both stimulation (p < 0.05) and stimulation number (p < 0.005). Normalized TWA showed reproducible peak reductions at both days within 35 min after the initiation of tVNS (p < 0.05). Our observations suggest that tVNS has short-term effects on TWA, supporting the notion that vagus nerve stimulation has a beneficial impact on electrical cardiac properties.

Differential Regulation of Wnt/ß-catenin Signaling in Acute and Chronic Epilepsy in Repeated Low Dose Lithium-Pilocarpine Rat Model of Status Epilepticus.

Epilepsy is a chronic neurological complication characterized by unprovoked seizure episodes due to the imbalance between excitatory and inhibitory neurons. The epileptogenesis process has been reported to be involved in chronic epilepsy however, the mechanism underlying epileptogenesis remains unclear. Recent studies have shown the possible involvement of Wnt/ß-catenin signaling in the neurogenesis and neuronal reorganization in epileptogenesis. In this study, we used repeated low dose lithium-pilocarpine model of status epilepsy (SE) to study the involvement of Wnt/ß-catenin signaling at acute and chronic stages post SE induction. The acute study ranged from day 0 to day 28 post SE induction and the chronic study ranged from day 0 to day 56 post SE induction. Several neurobehavioral parameters and seizure score and seizure frequency was analysed until the end of the study. The proteins involved in the regulation of Wnt/ß-catenin signaling and downstream cascading were analysed using western blot and quantitative real-time PCR analysis. The Wnt/ß-catenin pathway was found inactive in acute SE, while the same was found activated at the chronic stage. Our findings suggest that the activated Wnt/ß-catenin signaling in chronic epilepsy might be the possible mechanism underlying epileptogenesis as indicated by increased neuronal count, increased synaptic density, astrogliosis and apoptosis in chronic epilepsy. These findings can help target the Wnt/ß-catenin pathway differentially depending upon the type of epilepsy. The acute stage characterized by SE can be improved by targeting GSK-3ß levels and the chronic stage characterized by temporal lobe epilepsy can be improved by targeting ß-catenin and disheveled proteins.

Successful epilepsy surgery in two cases with multiple sclerosis.

Brain surgery is the only curative treatment for people with focal epilepsy, but it is unclear whether this induces active disease in multiple sclerosis (MS). This creates a barrier to evaluate MS patients for epilepsy surgery. We present two cases of successful epilepsy surgery in patients with pharmacoresistant epilepsy and stable MS and give an overview of the existing literature. (1) a 28-year-old woman with seizures arising from a right basal temporo-occipital ganglioglioma was seizure-free after surgery, without MS relapse but with one new MS lesion postsurgically. (2) a 46-year-old woman with seizures arising from a natalizumab-associated progressive multifocal leukoencephalopathy (PML) lesion in the right frontal lobe was seizure-free after surgery preceded by extraoperative subdural electrocorticography, with new subclinical MS lesions. We are the first to report brain surgery in a PML survivor. Both patients stabilized radiologically after initiating second-line therapies. Successful epilepsy surgery can substantially increase the quality of life in patients with pharmacoresistant epilepsy and MS. With increasing survival rates of brain tumors and PML, the risk-benefit ratio of epilepsy surgery compared to a potential MS relapse after surgery becomes critically important. Shared decision-making is valuable for balancing the risks related to both diseases.

Reactive A1 Astrocyte-Targeted Nucleic Acid Nanoantiepileptic Drug Downregulating Adenosine Kinase to Rescue Endogenous Antiepileptic Pathway.

Resistance to traditional antiepileptic drugs is a major challenge in chronic epilepsy treatment. MicroRNA-based gene therapy is a promising alternative but has demonstrated limited efficacy due to poor blood-brain barrier permeability, cellular uptake, and targeting efficiency. Adenosine is an endogenous antiseizure agent deficient in the epileptic brain due to elevated adenosine kinase (ADK) activity in reactive A1 astrocytes. We designed a nucleic acid nanoantiepileptic drug (tFNA-ADKASO@AS1) based on a tetrahedral framework nucleic acid (tFNA), carrying an antisense oligonucleotide targeting ADK (ADKASO) and A1 astrocyte-targeted peptide (AS1). This tFNA-ADKASO@AS1 construct effectively reduced brain ADK, increased brain adenosine, mitigated aberrant mossy fiber sprouting, and reduced the recurrent spontaneous epileptic spike frequency in a mouse model of chronic temporal lobe epilepsy. Further, the treatment did not induce any neurotoxicity or major organ damage. This work provides proof-of-concept for a novel antiepileptic drug delivery strategy and for endogenous adenosine as a promising target for gene-based modulation.

Evaluation of repeated ghrelin administration on seizures, oxidative stress and neurochemical parameters in pentyleneterazole induced kindling in rats.

Introduction: Epileptic seizures are thought to be caused by the impaired balance between excitatory (glutamate) and inhibitor [gamma amino butyric acid (GABA)] neurotransmitters in the brain. Neuropeptides have potent modulator properties on these neurotransmitters.Objective: Ghrelin exerts anticonvulsant effects in an acute pentylenetetrazole (PTZ) model. However, the effect of repeated ghrelin injections in chronic pentylenetetrazole kindling model is not known. In this study, the effects of repeated ghrelin administration on seizure scores, working memory, locomotor activity, oxidative biomarkers, and neurochemical parameters in PTZ kindling in rats was examined.Methods: For this purpose, 35 mg/kg of PTZ was administered intraperitoneally to the experimental groups. The rats also received physiological saline/diazepam or ghrelin before each PTZ injection. After behavioural analysis (Y-maze, rotarod, and locomotor activity tests), biochemical and neurochemical analyses were conducted using ELISA.Results: PTZ administration induced progression in the seizure scores and all of the rats in the PS + PTZ group were kindled with the 20th injection. Ghrelin treatment significantly reduced the seizure scores. The difference among the groups in terms of the Y-maze, locomotor activity, and rotarod tests was nonsignificant. PTZ administration significantly decreased the brain GABA, CAT, and AChE levels, and increased the MDA, NO, and protein carbonyl levels. Repeated ghrelin treatment ameliorated the GABA, AChE, CAT, MDA, NO, and protein carbonyl levels.Conclusion: Taken together, the results indicated that repeated ghrelin treatment had antioxidant, and anticonvulsant activity on PTZ kindling in rats.

Anticonvulsant Effect of Carbenoxolone on Chronic Epileptic Rats and Its Mechanism Related to Connexin and High-Frequency Oscillations.

Objective: This study was designed to investigate the influence and mechanism of gap junction carbenoxolone (CBX) on dynamic changes in the spectral power of ripples and fast ripples (FRs) in the hippocampus of chronic epileptic rats. Methods: The lithium-pilocarpine (PILO) status epilepticus (SE) model (PILO group) and the CBX pretreatment model (CBX + PILO group) were established to analyze dynamic changes in the spectral power of ripples and FRs, and the dynamic expression of connexin (CX)26, CX32, CX36, and CX43 in the hippocampus of chronic epileptic rats. Results: Within 28 days after SE, the number of spontaneous recurrent seizures (SRSs) in the PILO group was significantly higher than that in the CBX + PILO group. The average spectral power of FRs in the PILO group was significantly higher than the baseline level at 1 and 7 days after SE. The average spectral power of FRs in the PILO group was significantly higher than that in the CBX + PILO group at 1, 7, and 14 days after SE. Seizures induced an increase in CX43 expression at 1 and 7 days after SE, but had no significant effect on CX26, CX36, or CX32. CBX pretreatment did not affect the expression of CXs in the hippocampus of normal rats, but it inhibited the expression of CX43 in epileptic rats. The number of SRSs at 2 and 4 weeks after SE had the highest correlation with the average spectral power of FRs; the average spectral power of FRs was moderately correlated with the expression of CX43. Conclusion: The results of this study indicate that the energy of FRs may be regulated by its interference with the expression of CX43, and thus, affect seizures. Blocking the expression of CX43 thereby reduces the formation of pathological high-frequency oscillations (HFOs), making it a promising strategy for the treatment of chronic epilepsy.

Long-term seizure outcomes in patients with autoimmune encephalitis: A prospective observational registry study update.

OBJECTIVE: This study was undertaken to update and evaluate long-term seizure outcomes in patients with autoimmune encephalitis (AE) based on a large cohort study with long follow-up. METHODS: In this prospective observational registry study, we analyzed data from patients with AE mediated by common types of neuronal surface antibodies (anti-N-methyl-d-aspartate receptor [NMDAR], anti-leucine-rich glioma-inactivated 1 [LGI1]/contactin-associated protein-like 2 [Caspr2], anti-γ-aminobutyric acid type B receptor [GABAB R]). All patients were recruited from the Department of Neurology at West China Hospital between October 2011 and June 2019, and data were collected prospectively on their demographic and clinical characteristics, treatment strategy, and seizure outcomes, with a median follow-up of 42 months (range = 6-93 months). Potential risk factors associated with seizure recurrence were also assessed. RESULTS: Of 320 AE patients, 75.9% had acute seizures, among whom >90% of patients had their last seizure within 12 months of disease onset. During our follow-up, 21 (9.3%) patients experienced seizure recurrence. Patients with anti-GABAB R encephalitis had a higher cumulative incidence of seizure recurrence than those with anti-NMDAR (log-rank p = .03) or anti-LGI1/Caspr2 encephalitis (log-rank p = .04). Among patients with anti-NMDAR encephalitis, women had a significantly higher cumulative incidence of seizure recurrence than men (log-rank p = .01). Interictal epileptiform discharges (IEDs) or seizures captured on continuous electroencephalogram (EEG) in the acute phase were identified as potential risk factors for seizure recurrence (p = .04, p = .007). Among 163 patients with ≥24 months of follow-up, five (3.1%) showed persistent seizures and required ongoing antiseizure medications despite aggressive immunotherapy. SIGNIFICANCE: Seizure recurrence occurred in a small number of patients and chronic epilepsy occurred in 3.1% of patients during prolonged follow-up. Across all types of AE, risk factors for seizure recurrence were IEDs or seizures captured on EEG in the acute phase; for anti-NMDAR encephalitis, female sex was also a risk factor.

Dynamic functional connectivity in modular organization of the hippocampal network marks memory phenotypes in temporal lobe epilepsy.

Temporal lobe epilepsy (TLE) is a network disorder with a high incidence of memory impairment. Memory processing ability highly depends on the dynamic coordination between distinct modules within the hippocampal network. Here, we investigate the relationship between memory phenotypes and modular alterations of dynamic functional connectivity (FC) in the hippocampal network in TLE patients. Then, 31 healthy controls and 66 TLE patients with hippocampal sclerosis were recruited. The patients were classified into memory-intact (MI, 35 cases) group and memory-deficit (MD, 31 cases) group, each based on individual's Wechsler Memory Scale-Revised score. The sliding-windows approach and graph theory analysis were used to analyze the hippocampal network based on resting state functional magnetic resonance imaging. Temporal properties and modular metrics were calculated. Two discrete and switchable states were revealed: a high modularized state (State I) and a low modularized state (State II), which corresponded to either anterior or posterior hippocampal network dominated pattern. TLE was prone to drive less State I but more State II, and the tendency was more obvious in TLE-MD. Additionally, TLE-MD showed more widespread alterations of modular properties compared with TLE-MI across two states. Furthermore, the dynamic modularity features had unique superiority in discriminating TLE-MD from TLE-MI. These findings demonstrated that state transitions and modular function of dissociable hippocampal networks were altered in TLE and more importantly, they could reflect different memory phenotypes. The trend revealed potential values of dynamic FC in elucidating the mechanism underlying memory impairments in TLE.

Immunoreactivity of Muscarinic Acetylcholine M2 and Serotonin 5-HT2B Receptors, Norepinephrine Transporter and Kir Channels in a Model of Epilepsy.

Epilepsy is characterized by an imbalance in neurotransmitter activity; an increased excitatory to an inhibitory activity. Acetylcholine (ACh), serotonin, and norepinephrine (NE) may modulate neural activity via several mechanisms, mainly through its receptors/transporter activity and alterations in the extracellular potassium (K+) concentration via K+ ion channels. Seizures may disrupt the regulation of inwardly rectifying K+ (Kir) channels and alter the receptor/transporter activity. However, there are limited data present on the immunoreactivity pattern of these neurotransmitter receptors/transporters and K+ channels in chronic models of epilepsy, which therefore was the aim of this study. Changes in the immunoreactivity of epileptogenesis-related neurotransmitter receptors/transporters (M2, 5-HT2B, and NE transporter) as well as Kir channels (Kir3.1 and Kir6.2) were determined in the cortex, hippocampus and medulla of adult Wistar rats by utilizing a Pentylenetetrazol (PTZ)-kindling chronic epilepsy model. Increased immunoreactivity of the NE transporter, M2, and 5-HT2B receptors was witnessed in the cortex and medulla. While the immunoreactivity of the 5-HT2B receptor was found increased in the cortex and medulla, it was decreased in the hippocampus, with no changes observed in the M2 receptor in this region. Kir3.1 and Kir6.2 staining showed increase immunoreactivity in the cerebral cortex, but channel contrasting findings in the hippocampus and medulla. Our results suggest that seizure kindling may result in significant changes in the neurotransmitter system which may contribute or propagate to future epileptogenesis, brain damage and potentially towards sudden unexpected death in epilepsy (SUDEP). Further studies on the pathogenic role of these changes in neurotransmitter receptors/transporters and K+ channel immunoreactivity may identify newer possible targets to treat seizures or prevent epilepsy-related comorbidities.

Intravenous infusion of bone marrow mononuclear cells promotes functional recovery and improves impaired cognitive function via inhibition of Rho guanine nucleotide triphosphatases and inflammatory signals in a model of chronic epilepsy.

Temporal lobe epilepsy is the most common form of intractable epilepsy in adults. More than 30% of individuals with epilepsy have persistent seizures and have drug-resistant epilepsy. Based on our previous findings, treatment with bone marrow mononuclear cells (BMMC) could interfere with early and chronic phase epilepsy in rats and in clinical settings. In this pilocarpine-induced epilepsy model, animals were randomly assigned to two groups: control (Con) and epileptic pre-treatment (Ep-pre-t). The latter had status epilepticus (SE) induced through pilocarpine intraperitoneal injection. Later, seizure frequency was assessed using a video-monitoring system. Ep-pre-t was further divided into epileptic treated with saline (Ep-Veh) and epileptic treated with BMMC (Ep-BMMC) after an intravenous treatment with BMMC was done on day 22 after SE. Analysis of neurobehavioral parameters revealed that Ep-BMMC had significantly lower frequency of spontaneous recurrent seizures (SRS) in comparison to Ep-pre-t and Ep-Veh groups. Hippocampus-dependent spatial and non-spatial learning and memory were markedly impaired in epileptic rats, a deficit that was robustly recovered by treatment with BMMC. Moreover, long-term potentiation-induced synaptic remodeling present in epileptic rats was restored by BMMC. In addition, BMMC was able to reduce abnormal mossy fiber sprouting in the dentate gyrus. Molecular analysis in hippocampal tissue revealed that BMMC treatment down-regulates the release of inflammatory cytokine tumor necrosis factor-α (TNF-α) and Allograft inflammatory factor-1 (AIF-1) as well as the Rho subfamily of small GTPases [Ras homolog gene family member A (RhoA) and Ras-related C3 botulinum toxin substrate 1 (Rac)]. Collectively, delayed BMMC treatment showed positive effects when intravenously infused into chronic epileptic rats.

Self-reported antiepilepsy medication adherence and its connection to perception of medication error.

Although 70% of people with epilepsy (PWE) achieve seizure freedom following an appropriate antiepileptic drug (AED) regime, evidence suggests that adherence to AEDs by PWE is suboptimal. Nonadherence to AEDs is associated with increased morbidity, mortality, emergency department visits, and hospitalizations, with reduced adherence also correlating to a lower quality of life, decreased productivity, and loss of employment. Furthermore, research indicates that medication errors which are widespread in chronic disease are less well studied in epilepsy but are likely also to contribute to avoidable disease morbidity and mortality. The goals of this project were to determine rates of medication adherence by self-reported questionnaire and its links to perceived medication error in a cohort of PWE attending a general epilepsy outpatient clinic. Following a plan-do-study-act cycle, it was found that the most appropriate methodology for conducting was in the form of a bespoke 9-item self-administered questionnaire. One hundred eighty-six PWE completed a nine-question questionnaire asking patients about their own medication adherence habits and their perception that they were previously exposed to medication error. This study found that 41% of respondents reported suboptimal adherence to AED therapy, while 28.5% of respondents self-reported that they unintentionally do not take their AED medication on an occasional, regular, or frequent basis. A 5.9% of respondents self-reported that they intentionally do not take their medication as prescribed. A 6% of respondents self-reported that they are both unintentionally and intentionally nonadherent to their AED therapy. No significant associations were demonstrated between age, sex, perceived effectiveness of medication, feelings of stigma/embarrassment, adverse effects or additional neurological comorbidities, and unintentional or intentional nonadherence. A 28.5% of respondents to the questionnaire reported that they perceived themselves to have been subjected to medication error. Prescribing errors were the most common form of perceived medication error, followed by dispensing errors, then administration errors. Significant associations were found between ineffective medication and feelings of stigma or embarrassment about epilepsy with perceived prescribing errors. Intentional nonadherence to medication was significantly associated with perceived dispensing errors.

Gliotransmission: A Novel Target for the Development of Antiseizure Drugs.

For more than a century, epilepsy has remained an incapacitating neurological disorder with a high incidence worldwide. Mesial temporal lobe epilepsy (TLE) is a common type of epilepsy without an effective pharmacological treatment. An increase in excitability and hypersynchrony of electrical neuronal activity during development are typically associated with an excitatory/inhibitory imbalance in the neuronal network. Astrocytes release gliotransmitters, which can regulate neuronal excitability and synaptic transmission; therefore, the classical neurocentric vision of the cellular basis of epileptogenesis has begun to change. Growing evidence suggests that the key contribution of astrocyte-to-neuron signaling in the mechanisms underlies the initiation, propagation, and recurrence of seizure activity. The aim of this review was to summarize current evidence obtained from experimental models that suggest how alterations in astroglial modulation of synaptic transmission and neuronal activity contribute to the development of this brain disease. In this article, we will summarize the main pharmacological, Ca2+-imaging, and electrophysiological findings in the gliotransmitter-mediated modulation of neuronal activity and their possible regulation as a novel cellular target for the development of pharmacological strategies for treating refractory epilepsies.

A Model of Chronic Temporal Lobe Epilepsy Presenting Constantly Rhythmic and Robust Spontaneous Seizures, Co-morbidities and Hippocampal Neuropathology.

Many animal prototypes illustrating the various attributes of human temporal lobe epilepsy (TLE) are available. These models have been invaluable for comprehending multiple epileptogenic processes, modifications in electrophysiological properties, neuronal hyperexcitability, neurodegeneration, neural plasticity, and chronic neuroinflammation in TLE. Some models have also uncovered the efficacy of new antiepileptic drugs or biologics for alleviating epileptogenesis, cognitive impairments, or spontaneous recurrent seizures (SRS). Nonetheless, the suitability of these models for testing candidate therapeutics in conditions such as chronic TLE is debatable because of a lower frequency of SRS and an inconsistent pattern of SRS activity over days, weeks or months. An ideal prototype of chronic TLE for investigating novel therapeutics would need to display a large number of SRS with a dependable frequency and severity and related co-morbidities. This study presents a new kainic acid (KA) model of chronic TLE generated through induction of status epilepticus (SE) in 6-8 weeks old male F344 rats. A rigorous characterization in the chronic epilepsy period validated that the animal prototype mimicked the most salient features of robust chronic TLE. Animals displayed a constant frequency and intensity of SRS across weeks and months in the 5th and 6th month after SE, as well as cognitive and mood impairments. Moreover, SRS frequency displayed a rhythmic pattern with 24-hour periodicity and a consistently higher number of SRS in the daylight period. Besides, the model showed many neuropathological features of chronic TLE, which include a partial loss of inhibitory interneurons, reduced neurogenesis with persistent aberrant migration of newly born neurons, chronic neuroinflammation typified by hypertrophied astrocytes and rod-shaped microglia, and a significant aberrant mossy fiber sprouting in the hippocampus. This consistent chronic seizure model is ideal for investigating the efficacy of various antiepileptic drugs and biologics as well as understanding multiple pathophysiological mechanisms underlying chronic epilepsy.

Embelin Prevents Seizure and Associated Cognitive Impairments in a Pentylenetetrazole-Induced Kindling Zebrafish Model.

Epilepsy is a neuronal disorder associated with several neurological and behavioral alterations characterized by recurrent spontaneous epileptic seizures. Despite having more than 20 anti-epileptic drugs (AEDs), they only provide a symptomatic treatment. As well as, currently available AEDs also displayed cognitive alterations in addition to retarding seizure. This leads to the need for exploring new molecules that not only retard seizure but also improve cognitive impairment. Embelin (EMB) is a benzoquinone derivative which has already demonstrated its pharmacological potentials against arrays of neurological conditions. The current study developed a chronic kindling model in adult zebrafish by using repeated administration of small doses of pentylenetetrazole (PTZ) and a single dose of Kainic acid (KA) to investigate the associated memory impairment. This has been done by using the three-axis maze which is a conventional method to test the learning ability and egocentric memory in zebrafish. As well as, the ameliorative potential of EMB has been evaluated against chronic epilepsy-related memory alterations. Moreover the expression level of pro-inflammatory genes such as C-C motif ligand 2 (CCL2), toll-like receptor-4 (TLR4), tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interferon-γ (IFN-γ) were evaluated. The level of several neurotransmitters such as γ-aminobutyric acid (GABA), acetylcholine (Ach) and glutamate (Glu) was evaluated by liquid chromatography-mass spectrometry (LC-MS). The results showed that daily dose of PTZ 80 mg/kg for 10 days successfully induces a kindling effect in zebrafish, whereas the single dose of KA did not. As compared to control, the PTZ and KA group demonstrates impairment in memory as demonstrated by the three-axis maze. The PTZ group treated with a series of EMB doses (ranging from 0.156 to 0.625 mg/kg) was found to have retarded seizure as well as significantly reduces epilepsy-induced memory alteration. In addition, EMB treatment reduces the expression of inflammatory markers implicating its anti-inflammatory potential. Moreover, levels of GABA, Ach, and glutamate are increased in EMB administered group as compared to the PTZ administered group. Overall, findings demonstrate that EMB might be a potential candidate against chronic epilepsy-related cognitive dysfunction as EMB prevents the seizures, so we expect it to prevent the associated neuroinflammation and learning deficit.

Parents' experiences of videoconference as a tool for multidisciplinary information exchange for children with epilepsy and disability.

AIMS AND OBJECTIVES: To explore the parents' experiences with the multidisciplinary information exchange between different levels of the health- social and school services using videoconference. BACKGROUND: Children with epilepsy and disability are in need of long-term multidisciplinary help and support. The information exchange between the child's providers of support is challenging. Scant attention has been paid to the parents' experiences of the information exchange. DESIGN: A qualitative study with a phenomenological-hermeneutical research approach. METHOD: Children with epilepsy and disability had undergone a multidisciplinary assessment in a hospital in the tertiary health service followed by information exchange with each child's local support service using videoconference. Five parents were interviewed individually within a week after the videoconference. The COREQ checklist was used in the process of reporting on the empirical material. RESULTS: The increased local participation in the videoconference and the knowledge translation between the professionals made the parents save time, as they did not have to explain the written reports to each provider locally. The impact of technology created an emotional distance to the person on the screen and the information exchanged that some enjoyed while others disliked. The quality of the relationships to the professionals seemed to be crucial for the parents to feel safe talking about sensitive tasks. CONCLUSION: The parents prefer videoconference as a tool for information exchange to traditional face-to-face meetings as it enables discussions between professionals that might prevent treatment misunderstandings. They experience the method as time-saving and patient-centred. RELEVANCE TO CLINICAL PRACTICE: Professionals should be aware of the possible side effects of the impact of technology that might affect the interaction and the information exchange in a negative way. The findings are likely to be transferable beyond the current context.

Long-term monotherapy treatment with vitamin E reduces oxidative stress, but not seizure frequency in rats submitted to the pilocarpine model of epilepsy.

The imbalance between antioxidant system and reactive oxygen species (ROS) generation is related to epileptogenesis, neuronal death, and seizure frequency. Treatment with vitamin E has been associated with neuroprotection and control of seizures. In most experimental studies, vitamin E treatment has short duration. Therefore, the aim of this study was to verify the role of long-term treatment with vitamin E in rats submitted to the pilocarpine model of epilepsy. Rats were divided into two main groups: control (Ctr) and pilocarpine (Pilo). Each one was subdivided according to treatment: vehicle (Ctr V and Pilo V) or vitamin E at dosages of 6 IU/kg/day (Ctr E6 and Pilo E6) or 60 IU/kg/day (Ctr E60 and Pilo E60). Treatment lasted 120 days from status epilepticus (SE). There were no statistical differences concerning treatment in the Ctr group for all variables, so the data were grouped. Carbonyl content in the hippocampus of Pilo V and Pilo E6 was higher compared with that of the Ctr group (8 ±â€¯1.5, 7.1 ±â€¯1, and 3.1 ±â€¯0.3 nmol carbonyl/mg protein, respectively for Pilo V, Pilo E6, and Ctr; p < 0.05). Carbonyl content was restored to control values in Pilo E60 rats (4.2 ±â€¯1.1 and 3.1 ±â€¯0.3 nmol carbonyl/mg protein, respectively for Pilo E60 and Ctr; p > 0.05). The volume of the hippocampal formation (6.5 ±â€¯0.3, 6.6 ±â€¯0.4, 6.3 ±â€¯0.3, and 7.4 ±â€¯0.2, respectively for Pilo V, Pilo E6, Pilo E60, and Ctr) and subfields CA1 (1.6 ±â€¯0.1, 1.4 ±â€¯0.2, 1.5 ±â€¯0.1, and 2 ±â€¯0.05, respectively for Pilo V, Pilo E6, Pilo E60, and Ctr) and CA3 (1.7 ±â€¯0.1, 1.5 ±â€¯0.2, 1.4 ±â€¯0.1, and 2 ±â€¯0.1, respectively for Pilo V, Pilo E6, Pilo E60, and Ctr) was reduced in the Pilo group regardless of treatment. Parvalbumin immunostaining was increased in the hilus of the Pilo E60 group compared with that in the Ctr group (26 ±â€¯2 and 39.6 ±â€¯8.3 neurons, respectively for Ctr and Pilo E60). No difference was found in seizure frequency and Neo-Timm staining. Therefore, long-term treatment with 60 IU/kg/day of vitamin E prevented oxidative damage in the hippocampus and increased hilar parvalbumin expression in rats with epilepsy without a reduction in seizure frequency.

Protective Role of L-3-n-Butylphthalide in Cognitive Function and Dysthymic Disorders in Mouse With Chronic Epilepsy.

Epilepsy is a common neurological disease with recurrent seizures and neurobehavioral comorbidities, including cognitive impairment and psychiatric disorders. Recent studies suggest that L-3-n-butylphthalide (NBP), an extract from the seeds of Apium graveolens Linn. (Chinese celery), ameliorates cognitive dysfunction in ischemia and/or Alzheimer's disease animal models. However, little is known about the role of NBP in epilepsy and the associated comorbidities. Here, using a pilocarpine-induced chronic epileptic mouse model, we found that NBP supplement not only alleviated seizure severity and abnormal electroencephalogram, but also rescued cognitive and emotional impairments in these epileptic mice. The possible underlying mechanisms may be associated with the protective role of NBP in reducing neuronal loss and in restoring the expression of neural synaptic proteins such as postsynaptic density protein 95 (PSD95) and glutamic acid decarboxylase 65/67 (GAD65/67). In addition, NBP treatment increased the transcription of neuroprotective factors, brain-derived neurotrophic factor and Klotho. These findings suggest that NBP treatment may be a potential strategy for ameliorating epileptogenesis and the comorbidities of cognitive and psychological impairments.

Prospects of Cannabidiol for Easing Status Epilepticus-Induced Epileptogenesis and Related Comorbidities.

The hippocampus is one of the most susceptible regions in the brain to be distraught with status epilepticus (SE) induced injury. SE can occur from numerous causes and is more frequent in children and the elderly population. Administration of a combination of antiepileptic drugs can abolish acute seizures in most instances of SE but cannot prevent the morbidity typically seen in survivors of SE such as cognitive and mood impairments and spontaneous recurrent seizures. This is primarily due to the inefficiency of antiepileptic drugs to modify the evolution of SE-induced initial precipitating injury into a series of epileptogenic changes followed by a state of chronic epilepsy. Chronic epilepsy is typified by spontaneous recurrent seizures, cognitive dysfunction, and depression, which are associated with persistent inflammation, significantly waned neurogenesis, and abnormal synaptic reorganization. Thus, alternative approaches that are efficient not only for curtailing SE-induced initial brain injury, neuroinflammation, aberrant neurogenesis, and abnormal synaptic reorganization but also for thwarting or restraining the progression of SE into a chronic epileptic state are needed. In this review, we confer the promise of cannabidiol, an active ingredient of Cannabis sativa, for preventing or easing SE-induced neurodegeneration, neuroinflammation, cognitive and mood impairments, and the spontaneous recurrent seizures.

Effective clinical classification of chronic epilepsy into focal and generalized: A cross sectional study.

PURPOSE: Investigations such as EEG and brain imaging are often difficult to obtain in primary care settings of resource-limited regions impacting millions of epilepsy patients. We wanted to test the hypothesis that classification of chronic epilepsy into focal and generalized based on clinical history and examination alone would be comparable to making such a classification with additional inputs from EEG and brain imaging. METHODS: Two investigators independently classified consecutive chronic epilepsy patients into focal, generalized and unclassified epilepsy. Investigator 1 made this determination using clinical history and examination alone whereas Investigator II additionally used EEG and brain imaging too. We calculated inter observer agreement between the two investigators and also looked at the predictors of focal and generalized epilepsy. RESULTS: Five hundred and twelve patients were recruited. Inter observer agreement between the two investigators in making the focal versus generalized classification was 96.8%, kappa 0.91 (p<0.0001). When EEG and neuroimaging findings were added to clinical information, there was a change in classification in 3.2% patients. Several predictors of focal and generalized epilepsy were identified. CONCLUSIONS: Classification of chronic epilepsy into focal and generalized can be done reliably in most patients using clinical information alone. Investigating chronic epilepsy patients with EEG and brain imaging may not be necessary in every patient. The results of our study are especially significant for epilepsy patients living in resource-limited regions where such investigations may not always be available.

MicroRNA expression profiles in chronic epilepsy rats and neuroprotection from seizures by targeting miR-344a.

MicroRNA (miRNA) is believed to play a crucial role in the cause and treatment of epilepsy by controlling gene expression. However, it is still unclear how miRNA profiles change after multiple prolonged seizures and aggravation of brain injury in chronic epilepsy (CE). To investigate the role of miRNA in epilepsy, we utilized the CE rat models with pentylenetetrazol (PTZ) and miRNA profiles in the hippocampus. miRNA profiles were characterized using miRNA microarray analysis and were compared with the rats in the sham group, which received 0.9% physiological saline treatment at the same dose. Four up-regulated miRNAs (miR-139-3p, -770-5p, -127-5p, -331-3p) and 5 down-regulated miRNAs (miR-802-5p, -380-5p, -183-5p, -547-5p, -344a/-344a-5p) were found in the CE rats (fold change >1.5, P<0.05). Three of the dysregulated miRNAs were validated by quantitative real-time polymerase chain reaction, which revealed an outcome consistent with the initial results of the miRNA microarray analyses. Then, miR-344a agomir was intracerebroventricularly injected and followed by PTZ induction of CE models to investigate the effect of miR-344a in chronic neocortical epileptogenesis. After miRNA-344a agomir and scramble treatment, results showed a restoration of seizure behavior and a reduction in neuron damage in the cortex in miRNA-334a agomir treated rats. These data suggest that miRNA-344a might have a small modulatory effect on seizure-induced apoptosis signaling pathways in the cortex.